title: MR-1 modulates proliferation and migration of human hepatoma HepG2 cells through myosin light chains-2 (MLC2)/focal adhesion kinase (FAK)/Akt signaling pathway.
abstract: The key of cell migration process on solid substrates is phosphorylation of myosin light chain-2 (MLC2), which is implicated in a variety of intracellular functions. The previous data show that MLC2 interacts with a novel human gene, myofibrillogenesis regulator 1 (MR-1). Here, we reported that MR-1 was specially overexpressed in human hepatoma HepG2 cells. Transient treatment of cells with small interfering RNA (siRNA) against MR-1 or stable transfection of cells with plasmid expressing MR-1-siRNA led to inhibitions of cell proliferation, migration, and adhesion. Following down-regulation of MR-1, the phosphorylations of MLC2, focal adhesion kinase (FAK), and Akt were dramatically decreased, and the formation of stress fiber was destroyed by MR-1-siRNAs in hepatoma HepG2 cells. In addition, exogenous MR-1-induced as well as inherent phosphorylations of FAK and Akt were decreased by MLC kinase (MLCK) inhibitor, and F-actin polymerization inhibitor also decreased phosphorylations of FAK and Akt. Correspondingly, MR-1-enhanced migration of cells was also inhibited by these two inhibitors. These indicated that MLC2 activation and intact actin cytoskeleton were pivotal for MR-1 function. In vivo data showed that MR-1-siRNA markedly inhibited growth of human HepG2. This study suggested that overexpression of MR-1 was associated with cancer cell proliferation and migration through MLC2 and that MR-1 might be a potential cancer therapeutic target.
authors.affiliation: Department of Oncology, Institute of Medicinal Biotechnology, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Kaihuan
authors.initials: K
authors.lastname: Ren
authors.forename: Haixia
authors.initials: H
authors.lastname: Jin
authors.forename: Chunjing
authors.initials: C
authors.lastname: Bian
authors.forename: Hongwei
authors.initials: H
authors.lastname: He
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhang
authors.forename: Yiguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Rong-guang
authors.initials: RG
authors.lastname: Shao
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D024722:Cardiac Myosins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D009124:Muscle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018994:Myosin Light Chains / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D022502:Stress Fibers / Q000378:metabolism
chemical_list: D009124:Muscle Proteins; D018994:Myosin Light Chains; C495444:PNKD protein, human; D034741:RNA, Small Interfering; C107184:myosin light chain 2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D024722:Cardiac Myosins